Institute of Radiation Physics, University Hospital and University of Lausanne, Lausanne, Switzerland; Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland.
Radiation Oncology Laboratory, Department of Radiation Oncology, Lausanne, University Hospital and University of Lausanne, Lausanne, Switzerland.
Radiother Oncol. 2024 Dec;201:110539. doi: 10.1016/j.radonc.2024.110539. Epub 2024 Sep 17.
This study aimed to investigate the radiochemical oxygen depletion (ROD) in vivo by directly measuring oxygen levels in various mouse tissues during ultra-high dose rate (UHDR) irradiation at clinically relevant doses and dose rates.
Mice bearing subcutaneous human glioblastoma (U-87 MG) tumors were used for tumor and normal tissue (skin, muscle, brain) measurements. An oxygen-sensitive phosphorescent probe (Oxyphor PtG4) was injected into the tissues, and oxygen levels were monitored using a fiberoptic phosphorometer during UHDR irradiation with a 6 MeV electron linear accelerator (LINAC). Dose escalation experiments (10-40 Gy) were performed at a dose rate of 1300 Gy/s, and dose rate escalation experiments were conducted at a fixed dose of 40 Gy with dose rates ranging from 2 to 101 Gy/s.
Radiation-induced change in tissue oxygenation (ΔpO) increased linearly with dose and correlated with baseline tissue oxygenation levels in the range of 0 - 30 mmHg. At higher baseline tissue oxygenation levels, such as those observed in muscle and brain, there was no corresponding increase in ΔpO. When we modulated dose rate, ΔpO increased steeply up to ∼ 20 Gy/s and plateaued thereafter. The relationship between ΔpO and dose rate showcases the interplay between ROD and reoxygenation.
While UHDR irradiation induces measurable oxygen depletion in tissues, the observed changes in oxygenation levels do not support the hypothesis that ROD-induced radioresistance is responsible for the FLASH tissue-sparing effect at clinically relevant doses and dose rates. These findings highlight the need for further investigation into alternative mechanisms underlying the FLASH effect.
本研究旨在通过直接测量临床相关剂量和剂量率下超高速率（UHDR）照射时各种小鼠组织中的氧耗水平，研究体内放射性氧耗（ROD）。
采用皮下荷人胶质母细胞瘤（U-87 MG）肿瘤的小鼠进行肿瘤和正常组织（皮肤、肌肉、大脑）测量。将氧敏磷光探针（Oxyphor PtG4）注入组织，并用光纤磷光计在 6 MeV 电子直线加速器（LINAC）下进行 UHDR 照射时监测氧水平。在剂量率为 1300 Gy/s 时进行剂量递增实验（10-40 Gy），在固定剂量为 40 Gy 时进行剂量率递增实验，剂量率范围为 2-101 Gy/s。
组织氧合变化（ΔpO）随剂量呈线性增加，并与 0-30 mmHg 范围内的基线组织氧合水平相关。在较高的基线组织氧合水平下，如肌肉和大脑中观察到的水平，ΔpO 没有相应增加。当我们调节剂量率时，ΔpO 急剧增加至约 20 Gy/s 并随后趋于平稳。ΔpO 与剂量率之间的关系展示了 ROD 和再氧合之间的相互作用。
虽然 UHDR 照射会导致组织中可测量的氧耗，但观察到的氧合水平变化并不支持 ROD 诱导的放射抗性是导致临床相关剂量和剂量率下 FLASH 组织保护效应的假说。这些发现强调了需要进一步研究 FLASH 效应的替代机制。
